SPONTANEOUS ACTIVITY OF SOLITARY DOPAMINERGIC CELLS OF THE RETINA

Dopaminergic interplexiform amacrine cells were labeled in transgenic mice with human placental alkaline phosphatase and could therefore be identified after dissociation of the retina and used for whole-cell cu rrent and voltage clamp. In absence of synaptic inputs, dopaminergic a macrines spontaneously fired action potentials in a rhythmic pattern. This activity was remarkably robust in the face of inhibition of vario us voltage-dependent ion channels. It was minimally affected by extern al cesium or cobalt, suggesting no involvement of either the hyperpola rization-activated cation current I-h or voltage-dependent calcium cha nnels. Inhibiting calcium-activated potassium channels by charybdotoxi n or tetraethylammonium slowed the repolarizing phase of the action po tentials and eliminated a slow afterhyperpolarization but had a scarce effect on the frequency of spontaneous firing. Voltage-clamp experime nts showed that the interspike depolarization leading to threshold res ults from tetrodotoxin-sensitive sodium channels active at the intersp ike voltages of -60 to -40 mV. Because dopamine acts on distant target s in the retina, the pacemaker activity of dopaminergic amacrines may be necessary to ensure a tonic release of the modulator from their den dritic tree. Pacemaking is a property that this type of retinal amacri ne cell shares with the dopaminergic mesencephalic neurons, but the io nic mechanisms responsible for the spontaneous firing are apparently d ifferent.